April 26, 2005 — PORTLAND, Ore. --
Researchers at Oregon Health & Science University's Neurological
Sciences Institute (NSI) have shed light on the brain cell damage
caused by Alzheimer's disease. The researchers hope that by gaining a
better understanding of the disease's cellular impacts, progress can be
made towards developing a treatment. The research is reported in the
current edition of the Journal of Alzheimer's Disease, published by IOS
publishers.

While the cognitive and behavioral impacts of Alzheimer's can be
clearly witnessed in patients, the disease's cellular function and
methods for disrupting thought and memory have not been well
understood. By conducting this research, NSI scientists and their
collaborators have demonstrated how proteins involved in brain cell
communications, called synaptic proteins, decrease in the brains of
Alzheimer's patients when compared to healthy brains from people in the
same age range.

"More importantly, we found that the decrease of synaptic protein
levels in the frontal cortex of the brains of Alzheimer's patients was
more severe than in other portions of the brain," explained P.
Hemachandra Reddy, Ph.D., scientist at the Neurological Sciences
Institute and first and corresponding author of the paper. "Because the
frontal cortex is home to important brain functions such as reasoning,
planning, and abstract thought -- all affected by Alzheimer's -- this
finding appears to be significant. Furthermore, we noticed that
synaptic protein levels were even lower in the brains of patients in
the early stages of Alzheimer's disease. This suggests to us that the
loss of these important proteins happens very early in the disease
process."

One possible reason for the reduction of synaptic proteins is
mitochondrial dysfunction, a well-documented occurrence in Alzheimer's.
The researchers believe it's possible that defective mitochondria in
Alzheimer's neurons may not move effectively and may not supply
adequate levels of Adenosine Triphosphate (ATP). ATP is an important
cellular chemical that bonds at nerve terminals for normal neural
communication. The low levels of cellular ATP at nerve terminals may
lead to the loss of synapses and synaptic function, and may ultimately
cause cognitive decline in AD patients.

To conduct this research, Reddy and his colleagues studied 36 brain
specimens from both deceased Alzheimer's patients and deceased
non-Alzheimer's adults. The scientists specifically measured proteins
that take part in cellular communication. Cells communicate through
connections called synapses. Tiny electrical impulses pass from cell to
cell at these synapses. The process also involves a variety of proteins
that play various roles prior to, and following these cell
transmissions. These proteins are referred to as presynaptic and
postsynaptic proteins respectively. Of the seven proteins being
studied, data analysis revealed that the presynaptic proteins called
synaptophysin and rab 3a and the postsynaptic protein called
synaptopodin decreased the most in the brains of Alzheimer's patients.

"What this study helps demonstrate is that the decrease of synaptic
proteins is an early and important impact of Alzheimer's disease that
likely impacts one of the brains most important functions -
communication," added Reddy. ""Moreover we now know much more about
where these changes are taking place and what appear to be the proteins
most severely impacted to the disease."